Paper Citing NAMD - Abstract
Chang, Shan; He, Hong-Qiu; Shen, Lin; Wan, Hua
Understanding peptide competitive inhibition of botulinum neurotoxin a binding to SV2 protein via molecular dynamics simulations
BIOPOLYMERS, 103:597-608, OCT 2015
Botulinum neurotoxins (BoNTs) are known as the most toxic natural substances. Synaptic vesicle protein 2 (SV2) has been proposed to be a protein receptor for BoNT/A. Recently, two short peptides (BoNT/A-A2 and SV2C-A3) were designed to inhibit complex formation between the BoNT/A receptor-binding domain (BoNT/A-RBD) and the synaptic vesicle protein 2C luminal domain (SV2C-LD). In this article, the two peptide complex systems are studied by molecular dynamics (MD) simulations. The structural stability analysis indicates that BoNT/A-A2 system is more stable than SV2C-A3 system. The conformational analysis implies that the -sheet in BoNT/A-A2 system maintains its secondary structure but the two -strands in SV2C-A3 system have remarkable conformational changes. Based on the calculation of hydrogen bonds, hydrophobic interactions and cation- interactions, it is found that the internal hydrogen bonds play crucial roles in the structural stability of the peptides. Because of the stable secondary structure, the -sheet in BoNT/A-A2 system establishes effective interactions at the interface and inhibits BoNT/A-RBD binding to SV2C-LD. In contrast, without other -strands forming internal hydrogen bonds, the two isolated -strands in SV2C-A3 system become the random coil. This conformational change breaks important hydrogen bonds and weakens cation- interaction in the interface, so the complex formation is only partially inhibited by the two -strands. These results are consistent with experimental studies and may be helpful in understanding the inhibition mechanisms of peptide inhibitors. (c) 2015 Wiley Periodicals, Inc. Biopolymers 103: 597-608, 2015.
